The objectives of this project are to elucidate the biochemical mechanisms controlling the synthesis, storage, release, action and termination of action of neurotransmitters and to determine how genetic factors, environmental stimuli, or drugs influence these control mechanisms. The autonomic responses to stress appear to be genetically determined and differ among strains of rats. There is a relationship between the degree of behavioral activation and elevation of plasma catecholamines found during stress. In addition to differences in the magnitude of response of the central nervous system, in spontaneously hypertensive rats there is a greater sensitivity of the arterioles to norepinephrine, whether released from the nerve endings or administered intravenously. The central control of sympathodrenal activity involves cholinergic mechanisms which interact with dopaminergic neurones as well. Presynaptic alpha2-adrenoceptors are present on axonal sprouts. The affinity of various agonists to these receptors parallels their ability to inhibit release of 3H-NE.